Formamidines are basic molecules in the chemical industry. They are used in various industries and in particular for their applications as:                insecticides, pesticides, fungicides (J. Agric. Food Chem., 1977, Vol. 25, No. 3, 493-501; Ecotoxicology and Environmental Safety, 1996, 33, 163-167; J. Agric. Food Chem., 1969, Vol. 17, No. 3, 595-600; Bull. Environ. Contam. Toxicol., 2000, 65, 22-27),        pharmaceutical active principles (Clin. Pharmacol. Ther., 1999, 65, 369-376; Eur. J. Pharmacol., 1994, 288, 17-25),        synthesis reactants (Chem. Rev., 2011, 111, 2705-2733; Org. Lett., 2009, Vol. 11, No. 4, 1019-1022),        ligand for the preparation of catalysts (Eur. J. Org. Chem., 2010, 4893-4901).        
Thus, the present invention also relates to a process for the manufacture of insecticides, pesticides, fungicides, pharmaceutical products and catalysts comprising a stage of preparation of formamidines according to the process of the invention. Formamidines can also be used as intermediates in the synthesis of N-heterocyclic carbenes (Chem. Rev., 2011, 111, 2705-2733; Org. Lett., 2009, Vol. 11, No. 4, 1019-1022), or in the synthesis of alkaloids used in therapeutic chemistry (J. Org. Chem., 1996, 61, 573-580).
The synthesis of formamidines by reduction of organic ureas (also known as ureas) is an attractive synthesis route as ureas are stable and relatively nontoxic compounds which can be prepared in a simple way from carbon dioxide CO2 (Angew. Chem. Int. Ed., 2003, 42, 3257-3260; Green Chem., 2010, 12, 1811-1816).
However, the carbonyl functional groups of ureas are very difficult to reduce due to their thermodynamic stability (Angew. Chem. Int. Ed., 2011, 50, 11702-11705). Their reduction requires the use of powerful reducing agents, such as lithium aluminum hydride (LiAlH4) (J. Org. Chem., 1964, 29, 3697-3700; J. Org. Chem., 1950, 15, 1020-1022) or sodium borohydride (NaBH4) (Tetrahedron Lett., 1969, No. 9, 699-702), which exhibit the disadvantage of also reducing other functional groups which may be present.
The use of mild reducing agents, such as hydrogen, has ended in failure. This is because the urea is directly reduced to amines and methanol and the formamidine compound as such cannot be isolated (Angew. Chem. Int. Ed., 2011, 50, 11702-11705).
The inventors have discovered that the silanes corresponding to the following formula (III):
are attractive reducing agents for the reduction of ureas to give formamidines insofar as they are not very reactive, tolerated by functional groups (other than the carbonyl functional groups of the ureas), available commercially, stable and not very toxic (J. Chem. Soc., Perkin Trans. 1, 1999, 3381-3391).
Thus, the present invention relates to a process for the synthesis of formamidines of formula (I) by reduction of ureas of formula (II) by silanes of formula (In), according to the following reaction:

Conventionally, formamidines of general formula (I) are synthesized by condensation of a formamide of formula R1R2NCOH with an amine of formula R3NH2 in the presence of a strong dehydrating agent, such as thionyl chloride (SOCl2) (J. Med. Chem., 1988, 31, 1816-1820), phosphoryl trichloride (POCl3) (Eur. J. Org. Chem., 2010, 4893-4901; Bioorg. Med. Chem. Lett., 2010, 20, 6781-6784) or trifluoroacetic anhydride (Tetrahedron, 2006, 62, 5617-5625). These synthesis routes generally require moderate to strong heating which can range up to 180° C. and involve the handling of toxic reactants (SOCl2, POCl3, and the like).
An alternative route consists of the synthesis of formamidines by reaction between a primary amine and a trialkyl orthoformate, for example (EtO)3CH or (MeO)3CH (Org. Lett., 2009, Vol. 11, No. 4, 1019-1022; Synlett., 2011, No. 3, 405-409; J. Am. Chem. Soc., 1954, 76, 3978-3982).
Formamidines can also be obtained by reduction of the corresponding ureas. This method may appear attractive insofar as ureas can be easily prepared by condensation of amines with carbon dioxide CO2, which are molecules which are stable and easy to store. The synthesis of formamidines then requires the use of powerful reducing agents, such as LiAlH4, NaBH4, triethyl orthoformate ((EtO)3CH) (J. Am. Chem. Soc., 1955, 77, 5872-5877) or a dimethylaminoborane/trichlorophosphate mixture (Synthesis-Stuttgart, 1986, No. 3, 226-228).
The methods described in the state of the art thus require the use of reactants which are toxic (POCl3) or unstable with regard to water (LiAlH4, NaBH4, (EtO)3CH) and consequently difficult to store. Furthermore, they are not very selective and are incompatible with the presence of functional groups.
There thus exists a real need for a process for the preparation of formamidines which overcomes the disadvantages of the prior art and which makes it possible to obtain, in a single stage with a good yield and an excellent selectivity, formamidines by reduction of ureas by silanes, while not reducing the other functional groups which may be present on the urea.